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Cited by 47Fungal Infections and StudiesPneumocystis jirovecii pneumonia detection and treatmentInfectious Diseases and Tuberculosis

The DOI matches its Crossref record, with a small difference in title or year; 24 of the 25 references it cites were found in a registry or an index.

Reflexive Laboratory-Based Cryptococcal Antigen Screening and Preemptive Fluconazole Therapy for Cryptococcal Antigenemia in HIV-Infected Individuals With CD4 <100 Cells/µL: A Stepped-Wedge, Cluster-Randomized Trial

Open access
Meya, David B., Kiragga, Agnes N., Nalintya, Elizabeth, Morawski, Bozena M., Rajasingham, Radha, Park, Benjamin J., Mubiru, Anthony, Kaplan, Jonathan E., Manabe, Yukari C., Boulware, David R., on behalf of the ORCAS study team·2019·JAIDS Journal of Acquired Immune Deficiency Syndromes
DOI 10.1097/qai.0000000000001894PMC PMC6339522
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Abstract

Background: HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and preemptive fluconazole therapy, adjunctive to antiretroviral therapy (ART), on 6-month survival among persons with advanced HIV/AIDS. Methods: We enrolled HIV-infected, ART-naive participants with <100 CD4 cells/µL, in a stepped-wedge, cluster-randomized trial from July 2012 to December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with laboratory-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg+ participants received preemptive fluconazole therapy. We assessed 6-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps. Results: We included 1280 observational and 2108 interventional participants, of whom 9.3% (195/2108) were CrAg+. CD4-, time-, and stepped-wedge–adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (hazard ratio = 1.34; 95% confidence interval: 0.86 to 2.10; P = 0.20). Fewer participants initiated ART in the interventional (73%) versus the observational phase (82%, P < 0.001). When ART initiation was modeled as a time-dependent covariate or confounder, survival did not differ. However, 6-month mortality of participants with CrAg titers <1:160 and CrAg-negative patients did not differ. Patients with CrAg titers ≥1:160 had 2.6-fold higher 6-month mortality than patients with titers <1:160. Conclusions: We observed no overall survival benefit of the CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis seemed to be effective in patients with CrAg titer <1:160. A more aggressive approach is required for persons with CrAg titer ≥1:160.

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  • In more localized studies, clusters were often defined at the village or community level to capture the effects of interventions on specific populations.

    “In more localized studies, clusters were often defined at the village or community level to capture the effects of interventions on specific populations (28, 29, 39, 48, 54, 72, 78, 81, 103, 106, 108).”

    From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [39]

    The Methods, Study Design and Randomization (page not provided) defines the randomized clusters as clinics, not villages or communities. The paper evaluates the intervention across clinic sites, so it is contrary to the claimed cluster definition for this study. (LLM, conf=0.88)

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Authors
Meya, D. B., Kiragga, A. N., Nalintya, E., Morawski, B. M., Rajasingham, R., Park, B. J., Mubiru, A., Kaplan, J. E., Manabe, Y. C., Boulware, D. R., & on behalf of the ORCAS study team
Affiliations
  • University of Minnesota (US)
  • Infectious Diseases Institute (UG)
  • Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN;
  • Centers for Disease Control and Prevention (US)
  • Johns Hopkins University (US)
Corresponding author
  • Meya, David B.
  • Kiragga, Agnes N.
  • Nalintya, Elizabeth
  • Manabe, Yukari C.
ORCID
Venue
JAIDS Journal of Acquired Immune Deficiency Syndromes
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019-02-01
Volume
80
Issue
2
Pages
182-189
ISSN
1525-4135 (ISSN-L)
DOI
10.1097/qai.0000000000001894
PMC
PMC6339522
OpenAlex
W2899686258
Cited by
47
References
25
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 10 · 2019: 8
FWCI
4.49
Type
journal article
Language
en
Open access
Licence
Locations
  • JAIDS Journal of Acquired Immune Deficiency Syndromes (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • U.S. President’s Emergency Plan for AIDS Relief
  • Wellcome Trust (107742/Z/15/Z)
  • Centers for Disease Control and Prevention (U01GH000517)
  • National Institute of Allergy and Infectious Diseases (K23AI138851, P30AI094189)
  • Fogarty International Center (R25TW009345, D43TW009771)
  • National Institute of Neurological Disorders and Stroke (R01NS086312)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
  • Health Sciences › Medicine › Epidemiology › Pneumocystis jirovecii pneumonia detection and treatment
  • Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
Keywords
cryptococcal antigenemia, cryptococcosis, HIV infection, fluconazole, preemptive antifungal therapy, survival, CD4 count, antiretroviral therapy initiation, cryptococcal meningitis, Uganda
MeSH terms
Adult, Antifungal Agents, Antigens, Fungal, Cryptococcosis, Female, Humans, Male, Mass Screening, HIV Infections, Fluconazole, Cluster Analysis, AIDS-Related Opportunistic Infections, Guidelines as Topic, CD4 Lymphocyte Count, Chemoprevention

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